In the area of sperm metabolism we will isolate larger quantities of the seminal vesicle protein that is a specific inhibitor of calcium transport in spermatozoa. Antibodies to this protein will be used to develop a radioimmunoassay for the inhibitor of calcium transport to determine whether this is a ubiquitous regulator of Ca++ fluxes or whether it is confined to seminal vesicles and seminal fluid. The relation of alkali metal ion fluxes to the acrosomal reaction of mammalian spermatozoa will be examined using a sensitive method developed by Dr. D. F. Babcock. The role of acetyl carnitine in supporting the enhanced motility associated with sperm capacitation will be examined. The role of ferroactivator-4 in the synthesis of carnitine in testis and other tissues will be studied in detail. In the area of carbonhydrate metabolism we will continue the search for possible "second messengers" produced by the plasma membrane Alpha adrenergic receptor and those for vasopressin and angiotensin. The mechanism by which hepatocytes and perfused liver fail to respond to the "hyperglycemic" effect of 3-aminopicolinate will be studied as well as the hyperglycemic effects of lergotrile and related drugs. In the area of metabolic regulation, ferroactivators 3 and 4 will be purified and characterized. The protein to which FA-4 is bound will be isolated and its role in the hydroxylation of trimethyllysine and butyrobetaine will be examined. Ferroactivator 2 will be isolated from dog liver and its role in regulating dog liver P-enolpyruvate carboxykinase (PEPCK) will be examined. The mobilization of Fe++ from mitochondria by cytosolic Ca++ will be investigated in more detail as will the amount and cellular distribution of iron in liver and kidney of normal rats in comparison with those afflicted with metabolic disorders such as Fe++ deficiency anemia, excess dietary iron, diabetes, etc. Our long-term goal is to learn the cause and to find a rational method for prevention or treatment of diabetes.